Abundance and Localization of Progesterone Receptor Isoforms in Endometrium in Women With and Without Endometriosis and in Peritoneal and Ovarian Endometriotic Implants

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This study compared progesterone receptor isoforms in endometrium and endometriotic lesions, finding PR-A dominance in endometriosis and elevated PR-A in women with endometriosis.

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This tertiary-care in vitro immunohistochemical and immunoblot study compared progesterone receptor isoform abundance and localization (PR-A vs PR-B) in eutopic endometrium and endometriotic lesions versus disease-free peritoneum in reproductive-age women with surgically diagnosed endometriosis (n=18) and asymptomatic controls (n=20) sampled at late proliferative and early secretory phases. PR-A and PR-B were detected in eutopic endometrium and in peritoneal and ovarian endometriosis, but not in disease-free peritoneum, with peritoneal lesions showing a PR-A-predominant pattern and ovarian endometriosis showing both receptors. In eutopic endometrium, PR-A levels were significantly higher in women with endometriosis than in controls regardless of menstrual phase, and PR-A was also higher in ovarian versus peritoneal endometriosis. The study’s limitation is the relatively small cohort and that receptor analyses were performed on tissue obtained only at surgery across two cycle phases. This paper is centrally about endometriosis — it demonstrates a PR-A–dominant progesterone receptor state across endometriotic lesions and eutopic endometrium in women with endometriosis.

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Abstract

BackgroundSeveral studies suggest that resistance to progesterone may contribute to the pathophysiology of endometriosis. Progesterone mediates its biological activity via the 2 progesterone receptor (PR) isoforms (PR-A and PR-B). Effects of progesterone are determined by the PR-A:PR-B ratio such that a PR-B-dominant state promotes progesterone signaling, whereas a PR-A-dominant state decreases progesterone responsiveness. Our objective was to compare the abundance and cellular localization of the PR isoforms in endometrium and endometriotic lesions from women with and without peritoneal and ovarian endometriosis.MethodsThis in vitro study was conducted in a tertiary care facility. Reproductive-age women with surgically diagnosed endometriosis (n = 18) and asymptomatic control individuals (n = 20) were prospectively recruited at the late proliferative and the early secretory phases. At laparoscopy, samples of eutopic endometrium, peritoneal and ovarian endometriosis, and disease-free peritoneum were obtained for subsequent immunohistochemical and immunoblot analysis of PR-B and total PR localization and PR-A and PR-B abundance, respectively.ResultsThe PR-A and PR-B were detected in eutopic endometrium and in peritoneal and ovarian endometriosis but not in disease-free peritoneum from patients with and without endometriosis. In peritoneal endometriosis, PR-A was the predominant isoform detected, whereas both receptors were detected in ovarian endometriosis and eutopic endometrium. In eutopic endometrium, levels of PR-A were significantly elevated in women with endometriosis compared with women without disease, regardless of menstrual phase. The PR-A levels were significantly elevated in ovarian endometriosis compared with peritoneal endometriosis.ConclusionsEndometriotic lesions and eutopic endometrium from women with endometriosis are uniform in a PR-A-dominant state. The data suggest that menstrual efflux of a PR-A-dominant endometrial tissue into the peritoneal cavity may play a role in the pathophysiology of endometriosis.
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Abstract

Background Several studies suggest that resistance to progesterone may contribute to the pathophysiology of endometriosis. Progesterone mediates its biological activity via the 2 progesterone receptor (PR) isoforms (PR-A and PR-B). Effects of progesterone are determined by the PR-A:PR-B ratio such that a PR-B-dominant state promotes progesterone signaling, whereas a PR-A-dominant state decreases progesterone responsiveness. Our objective was to compare the abundance and cellular localization of the PR isoforms in endometrium and endometriotic lesions from women with and without peritoneal and ovarian endometriosis.

Methods

This in vitro study was conducted in a tertiary care facility. Reproductive-age women with surgically diagnosed endometriosis (n = 18) and asymptomatic control individuals (n = 20) were prospectively recruited at the late proliferative and the early secretory phases. At laparoscopy, samples of eutopic endometrium, peritoneal and ovarian endometriosis, and disease-free peritoneum were obtained for subsequent immunohistochemical and immunoblot analysis of PR-B and total PR localization and PR-A and PR-B abundance, respectively.

Results

The PR-A and PR-B were detected in eutopic endometrium and in peritoneal and ovarian endometriosis but not in disease-free peritoneum from patients with and without endometriosis. In peritoneal endometriosis, PR-A was the predominant isoform detected, whereas both receptors were detected in ovarian endometriosis and eutopic endometrium. In eutopic endometrium, levels of PR-A were significantly elevated in women with endometriosis compared with women without disease, regardless of menstrual phase. The PR-A levels were significantly elevated in ovarian endometriosis compared with peritoneal endometriosis.

Conclusions

Endometriotic lesions and eutopic endometrium from women with endometriosis are uniform in a PR-A-dominant state. The data suggest that menstrual efflux of a PR-A-dominant endometrial tissue into the peritoneal cavity may play a role in the pathophysiology of endometriosis. Similar content being viewed by others

References

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Expert Opinion Pharmacother. 2014;15(6):767–773. Author information Authors and Affiliations Corresponding author Rights and permissions About this article Cite this article Bedaiwy, M.A., Dahoud, W., Skomorovska-Prokvolit, Y. et al. Abundance and Localization of Progesterone Receptor Isoforms in Endometrium in Women With and Without Endometriosis and in Peritoneal and Ovarian Endometriotic Implants. Reprod. Sci. 22, 1153–1161 (2015). https://doi.org/10.1177/1933719115585145 Published: Issue date: DOI: https://doi.org/10.1177/1933719115585145

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Condition tags

endometriosis

MeSH descriptors

Endometriosis Endometrium Ovary Peritoneum Receptors, Progesterone Adult Biopsy Blotting, Western Case-Control Studies Cell Proliferation Endometriosis Endometriosis Endometriosis Endometriosis Endometrium Endometrium Endometrium Endometrium Female Humans

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